Cholesterol and Lipoproteins Flashcards Preview

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Flashcards in Cholesterol and Lipoproteins Deck (45):
1

LDL-R; mechanism

Receptor-mediated endocytosis; receptor recycled and apolipoprotein endosome fuses with lysosome

1

Metabolic syndrome symptoms

insulin resistance, hypertension, thrombosis, TAG:HDL ratio >4

2

Plants and sterols

Can't synthesize cholesterol; only stigmasterol, ergosterol

3

Atherogenic lipoproteins

ApoB - VLDL, LDL-C/P, Chylomicrons, IDL

4

Apolipoproteins and associated apoprotein

ApoB-48 - chylomicrons; synthesized in intestines ApoB-100 - synthesized in liver -VLDLs - along with other apoproteins -IDLs -LDLs ApoA-I and ApoA-II - HDL

4

Type IIa

Familial Hypercholesteronemia Lipoprotein - LDL Mutation - AD; LDL-R, apoB, PCSK9 Lipid Effect - TC > 275, LDL > 190

5

Polycystic kidney disease effects which lipid

Increases LDL

6

Type IV symptoms

Autosomal dominant Pancreatitis

8

Cholesterol vs cholesteryl esters

Cholesteryl esters - more non-polar, hydrophobic; found in lipoproteins

9

Effect of hypothyroidism

Increased LDL, Increased TAGs

10

Apolipoprotein lipid profile

Chylomicrons - highest TAG:Cholesterol ratio VLDLs - high TAG:Cholesterol ratio HDLs - Lowest TAG:cholesterol ratio

10

PCSK9; mechanism

Serine protease: Binds to EGF-A region of LDL-R Induces endocytosis of complex Lysosomal degradation

10

Most Important Ischemic Heart Disease Risk Factor

LDL:HDL ratio Lifestyle

10

Optimal levels of lipids

TC 40/50 Non-HDL

10

Type I lipid disorder

Hyperchylomicronemia Lipoprotein - Chylomicron Mutation - LPL or apoC-II/III Lipid Effect - TAGs > 2000

11

LDL-R; regulation

Thyroxine/estrogen - induce LDL-R expression SREBP/Scap - regulation of LDL-R expression PCSK9 - inhibit LDL-R; stimulate it's degradation

12

Apoproteins found in all apolipoproteins

ApoC-II = necessary for lipoprotein lipase activation ApoE = necessary for LDL-R/LRP interaction

13

Major TAG disorders

Type I, IIb, IV

15

ACAT; function

Esterification of cholesterol into cholesteryl esters

15

PCSK9; mutations

Overexpression = decreased LDL-R = increased cholesterol levels = Increased CVD risk Underexpression = increased LDL-R = decreased cholesterol levels = decreased CVD risk AD - gain-of-function = increased CVD risk

16

Type V

Hypertriglyceridemia Lipoprotein - VLDL, chylomicron Mutation - LPL or apoC-III Lipid Effect - TAGs > 1000

18

LPL Deficiency

Severe hypertriglyceridemia

19

LDL-R; ligand

ApoE

21

LDL-R; mutations

AD - hypercholesterolemia; mutation of ligand binding region

22

ACAT; types

ACAT-1 = sebaceous glands, macrophages, adrenocortical ACAT-2 = liver, intestines

23

Ranges of Lipids

TC = 200-350 = ASCVD risk LDL >100 = ASCVD risk HDL 1000 = pancreatitis

24

Type III

Dysbetalipoproteinemia Lipoprotein - VLDL, IDL Mutation - overexpression of ApoE-II Lipid Effect - TC/TAGs = 200-500

25

Major ASCVD disorders

Type IIa, IIb, III

26

Lipid panel includes?

TC, TAGs, HDL, LDL (calc), Non-HDL (calc) Can include - apoB, LDL-P

27

Type I symptoms

Autosomal recessive Pancreatitis, hepatosplenmegaly, xanthomas. No increased ASCVD risk

29

Regulation of LPL

High glycogen, fats = Induction of LPL for storage of lipids into adipose tissue Fasting = decreased LPL expression; prevents storage of lipids out of plasma

30

Cholesterol is a precursor for what

Gonads -pregnenlone to progesterone to androgens to estrogens Adrenal -progesterone to mineralcorticoids (aldosterone and corticosterone) and glucocorticoids Vitamin D -7-dehydrocholesterol to cholecalciferol (Vitamin D) Liver -7-hydroxycholesterol to bile acid

31

Type IV

Hypertriglyceridemia Lipoprotein - VLDL Mutation - LPL or apoC-III Lipid Effect - TAGs = 500-1000

32

Cholesterol synthesis; important steps

HMG-CoA Synthase -Acetyl-CoA + Acetoacetyl-CoA = HMG-CoA HMG-CoA Reductase -HMG-CoA + 2NADPH = mevalonate *Rate-limiting step

34

Cofactors of LPL

Heparin - anchors LPL to capillary endothelia IV heparin - used to displace LPL into plasma; for measuring LPL levels ApoC-II - obligatory cofactor

35

Function of LPL

To hydrolyze phospholipids: TAG to DAG to MAG

36

Location of LPL

Capillary endothelium; near adipose tissue, skeletal muscle, heart muscle, glands, etc.

36

Factors lowering HDL

o Insulin resistance/metabolic syndrome o Anabolic steroids o Trans-fats o Progestins o Smoking

37

Type IIa symptoms

Autosomal dominant Heterozygotes = TC = 300 mg/dL Homozygotes = TC = 700 mg/dL Accelerated atherosclerosis (MI before 20), xanthomas, corneal arcus

39

Lipoprotein w/ longest half-life

LDL

40

Type IIb

Familial Compound Hyperlipidemia Lipoprotein - VLDL, LDL Mutation - metabolic syndrome/insulin resistance; ApoB-100 Lipid Effect - TC = 100, TAGs = 200-500, HDL < 40/50 increased VLDL remnants and LDL-P

41

Factors increasing HDL

o Aerobic exercise o Alcohol o Estrogens

43

Metabolic Syndrome Criteria

add picture

44

Obstructive kidney disease affects which lipid

Increases LDL

45

What is the exogenous pathway of apolipoproteins

Dietary lipids in intestinal lumen (1) intestinal epithelial cell cytoplasm (2) esterification of cholesterol (3) efflux of plant sterols (4) chylomicron formation (5) transport of lipids to liver and tissues (6) chylomicron remnants 1 = NPC1L1 = influx of lipids into epithelial -ezetimibe targets NPC1L1 2 = ACAT-2 3 = ABCG5/8 = efflux of plant sterols out of cell -Mutation = sitosterolemia = xanthomas, increased CVD risk 4 = MTP = apoB-48 synthesized in intestine; MTP transports esters to apoB-48 5 = LDL-R/apoE 6 = processed by liver -apoB-48 degraded -other apoproteins recycled to HDL